Long-term hepatic memory for hypersensitivity to nitrofurantoin

Nitrofurantoin-induced hepatic injury has been established unequivocally as an entity by rechallenge experiences. We reviewed 12 previously reported cases in which rechallenge was described. The longest reported interval between initial injury and rechallenge-provoked injury was 4 yr. We report a 56-yr-old woman who experienced severe hepatocellular injury with brief low-dose administration of nitrofurantoin 17 yr after an initial hepatitis-like illness associated with ingestion of the drug. Despite a temporal relationship to nitrofurantoin administration and histologic features compatible with drug-induced hepatitis, the initial bout of hepatitis had been termed "infectious." Our case appears remarkable for the long interval between initial injury and rechallenge-induced injury. The severity of the hepatic injury seen on rechallenge underscores the concept that the inadvertent rechallenge can be dangerous. Failure to identify the first bout of hepatitis as nitrofurantoin-related, and failure to inform the patient about the possible relationship to nitrofurantoin, raises important risk-management concerns, because hepatic memory of nitrofurantoin hypersensitivity appears to be of long duration.